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Biomolecules
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The Value of Natural Compounds as Therapeutic Agents: 2nd Edition
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The Value of Natural Compounds as Therapeutic Agents: 2nd Edition

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Natural and Bio-derived Molecules".

Deadline for manuscript submissions: closed (15 January 2025) | Viewed by 14345

Special Issue Editor

Dr. Maria Beatrice Morelli

E-Mail Website
Guest Editor
School of Pharmacy, University of Camerino, 62032 Camerino, Italy
Interests: glioblastoma; TRP channel; mucolipins; autophagy; overall survival; transient receptor potential channels; tumor progression; chemotherapy resistance; cancer biology; cancer stem cell; circulating tumor cell; liquid biopsy; biomarkers; ion channel; natural compound; cannabinoids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Following a very successful first run, we are pleased to announce the launch of a second edition of our Special Issue, entitled “The Value of Natural Compounds as Therapeutic Agents II”.

Naturally occurring substances have long been used by humans for medicinal purposes as concoctions or concentrated extracts. At present, natural products are gaining popularity. A number of pathological conditions have been treated previously with plant-derived medicines, including cancer and inflammation.

Therefore, in this Special Issue, we aim to bring together the opinions of experts and scientists who work on natural compounds to gather information and data about their involvement in a wide variety of biological mechanisms at the cellular level. The Special Issue will predominantly focus on cellular processes, such as proliferation and survival, apoptosis, dormancy, differentiation, autophagy and senescence, migration, and invasion. Additionally, we are keen to publish analyses of soluble mediators involved with microenvironment modulation.

In summary, we would like to emphasize the existing evidence regarding the various potential advantages of plant extracts and plant extract-based products with regard to human health. Therefore, we encourage the submission of manuscripts that utilize structurally defined natural products or their derivatives, or well-characterized mixtures. We welcome original research articles, review articles, and communications.

Dr. Maria Beatrice Morelli
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural compound
  • acute and chronic conditions
  • cell proliferation
  • cell death
  • cell differentiation

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Related Special Issues

Published Papers (8 papers)

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Research

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18 pages, 2885 KiB  
Article
A Study of the Effects of Oleuropein and Polydatin Association on Muscle and Bone Metabolism
by Maria Beatrice Morelli, Cristina Aguzzi, Riccardo Rascioni and Fiorenzo Mignini
Biomolecules 2025, 15(5), 628; https://doi.org/10.3390/biom15050628 - 28 Apr 2025
Viewed by 257
Abstract
Sarcopenia and osteoporosis are age-related musculoskeletal pathologies that often develop in parallel, and numerous studies support the concept of a bone–muscle unit, where deep interaction between the two tissues takes place. In Mediterranean areas, the lowest incidence of osteoporosis within Europe is observed, [...] Read more.
Sarcopenia and osteoporosis are age-related musculoskeletal pathologies that often develop in parallel, and numerous studies support the concept of a bone–muscle unit, where deep interaction between the two tissues takes place. In Mediterranean areas, the lowest incidence of osteoporosis within Europe is observed, so the Mediterranean diet was suggested to play an important role. Consequently, in this study, oleuropein, a phenolic compound found in olive oil, and polydatin, another natural polyphenol found in the Mediterranean diet, were evaluated to determine their beneficial effects on bone and muscle metabolism. In human osteoblasts and skeletal muscle myoblasts, the effects were examined, and, after analyzing the cytotoxic effect to find non-toxic doses, the modulation of bone and muscle differentiation markers was evaluated at the gene and protein levels using PCR, Western blot, and immunohistochemistry. Interestingly, the compounds increased markers involved in osteoblast differentiation, such as osteocalcin, type I collagen, and dentin-sialo-phosphoprotein, as well as markers involved in myoblast differentiation, such as myogenic regulatory factors and creatine kinase. These effects were most noticeable when the compounds were administered together. These results suggest a beneficial role for oleuropein–polydatin association on bone and muscle tissue pathologies simultaneously. Full article
(This article belongs to the Special Issue The Value of Natural Compounds as Therapeutic Agents: 2nd Edition)
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19 pages, 4108 KiB  
Article
Petroselinic Acid from Apiaceae Family Plants Ameliorates Autoimmune Disorders Through Suppressing Cytosolic-Nucleic-Acid-Mediated Type I Interferon Signaling
by Yue Guo, Yun-Ying Wang, Yao Wang, Yan-Hong Liu, Jia-Yu Liu, Yan-Yan Shen, Ai-Ping Cao, Rui-Bo Wang, Bo-Yang Xie, Xin Pan, Ai-Ling Li, Tao Zhou, Na Wang, Qing Xia and Wei-Na Zhang
Biomolecules 2025, 15(3), 329; https://doi.org/10.3390/biom15030329 - 24 Feb 2025
Viewed by 539
Abstract
The recognition of cytosolic nucleic acids is a critical step in the host immune response against danger signals, such as molecular patterns from pathogens or tissue damage. Nonetheless, over-reactivity to self-nucleic acids leads to the sustained production of type I interferon (IFN), mediated [...] Read more.
The recognition of cytosolic nucleic acids is a critical step in the host immune response against danger signals, such as molecular patterns from pathogens or tissue damage. Nonetheless, over-reactivity to self-nucleic acids leads to the sustained production of type I interferon (IFN), mediated either by cGAS or RLR, contributing to the pathogenesis of certain autoimmune diseases, such as Aicardi–Goutières syndrome (AGS). Therefore, inhibiting excessive IFN production represents a potential therapeutic strategy for such autoimmune conditions. In this study, we discovered that petroselinic acid (PA), a natural compound isolated from Apiaceae family plants, effectively suppresses type I IFN production induced by cytosolic nucleic acids. Mechanistic investigations revealed that PA inhibits the phosphorylation of TBK1 and IRF3, which are key nodal proteins within the type I interferon pathway. Notably, molecular docking suggests potential binding between PA and cytosolic nucleic acid sensors, such as cGAS and RIG-I. Moreover, we found that PA effectively attenuates the expression of type I IFN and their downstream interferon-stimulated genes (ISGs) in models of AGS autoimmune disease characterized by excessive nucleic acid accumulation. Thus, our research identifies a natural compound that offers a promising strategy for treating autoimmune diseases resulting from aberrant self-nucleic acid recognition and the hyperactivation of type I interferon. Full article
(This article belongs to the Special Issue The Value of Natural Compounds as Therapeutic Agents: 2nd Edition)
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18 pages, 13688 KiB  
Article
Protective Effects of Bromelain in Testicular Torsion-Detorsion: Reducing Inflammation, Oxidative Stress, and Apoptosis While Enhancing Sperm Quality
by Seda Yakut, Merve Karabulut, Recep Hakkı Koca, Elif Erbaş, Seçkin Özkanlar, Berrin Tarakçı Gençer, Adem Kara and K. J. Senthil Kumar
Biomolecules 2025, 15(2), 292; https://doi.org/10.3390/biom15020292 - 15 Feb 2025
Cited by 2 | Viewed by 1077
Abstract
Inflammation and increased oxidative stress in testicular tissue are documented side effects of torsion of the testicles. The preventive role of Bromelain (Bro) against testicle torsion-induced ischemia/reperfusion (I/R) injury was investigated in this research. Five groups of six animals each were created: ischemia, [...] Read more.
Inflammation and increased oxidative stress in testicular tissue are documented side effects of torsion of the testicles. The preventive role of Bromelain (Bro) against testicle torsion-induced ischemia/reperfusion (I/R) injury was investigated in this research. Five groups of six animals each were created: ischemia, Ischemia+Reperfusion (I+R), Ischemia+Reperfusion+Bromelain (I+R+Bro; 10 mg/kg), control (sham), and Bromelain (Bro; 10 mg/kg). An I/R damage resulted from two hours of 720° clockwise twisting of the left testis. Blood samples and epididymal sperm were collected after reperfusion to analyze sperm parameters (recovery, motility, viability, and morphology) and cytokines that promote inflammation (IL-1β, IL-6, and TNF-α). Using Western blotting, testicular tissue was examined for histopathological alterations, antioxidant enzymes (GSH, SOD), lipid peroxidation (MDA), apoptosis, and survival-related proteins (TLR4, Caspase-3, Bcl-2, NRF-2, HO-1, PI3K, mTOR, AKT-1). While raising the activities of GSH and SOD, two antioxidant enzymes, Bro administration dramatically reduced MDA concentrations. The I+R+Bro group had significantly reduced amounts of cytokines that promoted inflammation compared to the I+R group. Bro’s protective properties are also attributed to proteins that are altered by it and participate in the apoptosis and survival of cells. Sperm morphology, motility, and concentration notably improved in the bromelain-treated group, according to spermatological examination. Testicular samples treated with bromelain showed less tissue damage according to histological evaluations than the untreated I+R group. These findings imply that Bro has anti-inflammatory, anti-apoptotic, and antioxidant qualities. It effectively reduces oxidative stress and inflammation by modulating the PI3K/Akt/mTOR and NRF-2/HO-1 pathways, hence minimizing I/R injury. Full article
(This article belongs to the Special Issue The Value of Natural Compounds as Therapeutic Agents: 2nd Edition)
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15 pages, 3793 KiB  
Article
Panduratin A Inhibits TNF Alpha-Stimulated Endothelial Cell Activation Through Suppressing the NF-κB Pathway
by Kriangkrai Kiatsoonthon, Nitchakarn Phimthong, Saranyapin Potikanond, Nitwara Wikan and Wutigri Nimlamool
Biomolecules 2025, 15(1), 34; https://doi.org/10.3390/biom15010034 - 30 Dec 2024
Viewed by 1021
Abstract
Upon exposure to inflammatory stimuli including TNF-α, endothelial cells are activated leading to the adhesion of monocytes to their surface. These events are involved in the pathophysiology of atherosclerosis. Since TNF-α activates the NF-κB pathway, which contributes to atherosclerosis, targeting this signaling pathway [...] Read more.
Upon exposure to inflammatory stimuli including TNF-α, endothelial cells are activated leading to the adhesion of monocytes to their surface. These events are involved in the pathophysiology of atherosclerosis. Since TNF-α activates the NF-κB pathway, which contributes to atherosclerosis, targeting this signaling pathway may help prevent the risk of developing the disease. The current study elucidated the inhibitory effect of panduratin A (PA) on TNF-α-induced endothelial activation and monocyte adhesion. We discovered that PA reduced the level of pro-inflammatory cytokine IL-6 and chemokine MCP-1 in the media collected from endothelial cells stimulated with TNF-α. In addition, PA inhibited the expression of ICAM-1 and VCAM-1 on the surface of TNF-α-induced endothelial cells resulting in a decrease in the number of monocytes attached to endothelial cell surface. Mechanistically, PA prevented IκB degradation and specifically suppressed NF-κB phosphorylation and nuclear translocation in endothelial cells. However, PA had no inhibitory effect on the phosphorylation of AKT, ERK1/2, p38, and JNK. Taken together, PA blocked the production of cytokine and chemokine, adhesion molecules, and monocyte adhesion in response to TNF-α stimulation, in part, through NF-κB inhibition. Our study suggests that PA may possibly be effective in blocking the pathophysiology of atherosclerosis. Full article
(This article belongs to the Special Issue The Value of Natural Compounds as Therapeutic Agents: 2nd Edition)
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22 pages, 2538 KiB  
Article
Cannabis sativa L. Extract Alleviates Neuropathic Pain and Modulates CB1 and CB2 Receptor Expression in Rat
by Joanna Bartkowiak-Wieczorek, Agnieszka Bienert, Kamila Czora-Poczwardowska, Radosław Kujawski, Michał Szulc, Przemysław Mikołajczak, Anna-Maria Wizner, Małgorzata Jamka, Marcin Hołysz, Karolina Wielgus, Ryszard Słomski and Edyta Mądry
Biomolecules 2024, 14(9), 1065; https://doi.org/10.3390/biom14091065 - 26 Aug 2024
Cited by 5 | Viewed by 2681
Abstract
Introduction: Cannabis sativa L. (CSL) extract has pain-relieving potential due to its cannabinoid content, so the effects of two CSL extracts on alleviating neuropathic pain were investigated in vivo. Methods and groups: Male Wistar rats (n = 130) were divided into groups and [...] Read more.
Introduction: Cannabis sativa L. (CSL) extract has pain-relieving potential due to its cannabinoid content, so the effects of two CSL extracts on alleviating neuropathic pain were investigated in vivo. Methods and groups: Male Wistar rats (n = 130) were divided into groups and received vincristine (0.1 mg/kg) and gabapentin (60 mg/kg) to induce and relieve neuropathic pain or CSL extracts (D and B). The mRNA and protein expression of the cannabinoid receptors type 1 and 2 (CB1R, CB2R) were evaluated in the cerebral cortex, hippocampus, and lymphocytes. Behavioural tests (Tail-Flick and von Frey) were performed on all animals. Results: VK-induced neuropathic pain was accompanied by decreased CB1R protein level and CB2R mRNA expression in the cortex. Gabapentin relieved pain and increased CB1R protein levels in the hippocampus compared to the vincristine group. Hippocampus CB1R protein expression increased with the administration of extract D (10 mg/kg, 40 mg/kg) and extract B (7.5 mg/kg, 10 mg/kg) compared to VK group. In the cerebral cortex CSL decreased CB1R protein expression (10 mg/kg, 20 mg/kg, 40 mg/kg of extract B) and mRNA level (5 mg/kg, 7.5 mg/kg of extract B; 20 mg/kg of extract D) compared to the VK-group.CB2R protein expression increased in the hippocampus after treatment with extract B (7.5 mg/kg) compared to the VK-group. In the cerebral cortex extract B (10 mg/kg, 20 mg/kg) increased CB2R protein expression compared to VK-group. Conclusion: Alterations in cannabinoid receptor expression do not fully account for the observed behavioural changes in rats. Therefore, additional signalling pathways may contribute to the initiation and transmission of neuropathic pain. The Cannabis extracts tested demonstrated antinociceptive effects comparable to gabapentin, highlighting the antinociceptive properties of Cannabis extracts for human use. Full article
(This article belongs to the Special Issue The Value of Natural Compounds as Therapeutic Agents: 2nd Edition)
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15 pages, 2511 KiB  
Article
Menthol Pretreatment Alleviates Campylobacter jejuni-Induced Enterocolitis in Human Gut Microbiota-Associated IL-10−/− Mice
by Markus M. Heimesaat, Luis Q. Langfeld, Niklas Schabbel, Nizar W. Shayya, Soraya Mousavi and Stefan Bereswill
Biomolecules 2024, 14(3), 290; https://doi.org/10.3390/biom14030290 - 29 Feb 2024
Cited by 1 | Viewed by 1994
Abstract
Human Campylobacter jejuni infections are of worldwide importance and represent the most commonly reported bacterial enteritis cases in middle- and high-income countries. Since antibiotics are usually not indicated and the severity of campylobacteriosis is directly linked to the risk of developing post-infectious complications, [...] Read more.
Human Campylobacter jejuni infections are of worldwide importance and represent the most commonly reported bacterial enteritis cases in middle- and high-income countries. Since antibiotics are usually not indicated and the severity of campylobacteriosis is directly linked to the risk of developing post-infectious complications, non-toxic antibiotic-independent treatment approaches are highly desirable. Given its health-promoting properties, including anti-microbial and anti-inflammatory activities, we tested the disease-alleviating effects of oral menthol in murine campylobacteriosis. Therefore, human gut microbiota-associated IL-10−/− mice were orally subjected to synthetic menthol starting a week before C. jejuni infection and followed up until day 6 post-infection. Whereas menthol pretreatment did not improve campylobacteriosis symptoms, it resulted in reduced colonic C. jejuni numbers and alleviated both macroscopic and microscopic aspects of C. jejuni infection in pretreated mice vs. controls. Menthol pretreatment dampened the recruitment of macrophages, monocytes, and T lymphocytes to colonic sites of infection, which was accompanied by mitigated intestinal nitric oxide secretion. Furthermore, menthol pretreatment had only marginal effects on the human fecal gut microbiota composition during the C. jejuni infection. In conclusion, the results of this preclinical placebo-controlled intervention study provide evidence that menthol application constitutes a promising way to tackle acute campylobacteriosis, thereby reducing the risk for post-infectious complications. Full article
(This article belongs to the Special Issue The Value of Natural Compounds as Therapeutic Agents: 2nd Edition)
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16 pages, 2875 KiB  
Article
Prophylactic Oral Application of Activated Charcoal Mitigates Acute Campylobacteriosis in Human Gut Microbiota-Associated IL-10−/− Mice
by Markus M. Heimesaat, Niklas Schabbel, Luis Q. Langfeld, Nizar W. Shayya, Soraya Mousavi and Stefan Bereswill
Biomolecules 2024, 14(2), 141; https://doi.org/10.3390/biom14020141 - 23 Jan 2024
Cited by 2 | Viewed by 2618
Abstract
The incidence of human Campylobacter jejuni infections is increasing worldwide. It is highly desirable to prevent campylobacteriosis in individuals at risk for severe disease with antibiotics-independent non-toxic compounds. Activated charcoal (AC) has long been used as an anti-diarrheal remedy. Here, we tested the [...] Read more.
The incidence of human Campylobacter jejuni infections is increasing worldwide. It is highly desirable to prevent campylobacteriosis in individuals at risk for severe disease with antibiotics-independent non-toxic compounds. Activated charcoal (AC) has long been used as an anti-diarrheal remedy. Here, we tested the disease-mitigating effects of oral AC versus placebo in human gut microbiota-associated (hma) IL-10−/− mice starting a week prior to C. jejuni infection. On day 6 post-infection, the gastrointestinal C. jejuni loads were comparable in both infected cohorts, whereas campylobacteriosis symptoms such as wasting and bloody diarrhea were mitigated upon AC prophylaxis. Furthermore, AC application resulted in less pronounced C. jejuni-induced colonic epithelial cell apoptosis and in dampened innate and adaptive immune cell responses in the colon that were accompanied by basal concentrations of pro-inflammatory mediators including IL-6, TNF-α, IFN-γ, and nitric oxide measured in colonic explants from AC treated mice on day 6 post-infection. Furthermore, C. jejuni infection resulted in distinct fecal microbiota shift towards higher enterobacterial numbers and lower loads of obligate anaerobic species in hma mice that were AC-independent. In conclusion, our pre-clinical placebo-controlled intervention study provides evidence that prophylactic oral AC application mitigates acute murine campylobacteriosis. Full article
(This article belongs to the Special Issue The Value of Natural Compounds as Therapeutic Agents: 2nd Edition)
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Review

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14 pages, 1511 KiB  
Review
Curcumin and Resveratrol: Nutraceuticals with so Much Potential for Pseudoachondroplasia and Other ER-Stress Conditions
by Karen L. Posey
Biomolecules 2024, 14(2), 154; https://doi.org/10.3390/biom14020154 - 27 Jan 2024
Cited by 10 | Viewed by 3045
Abstract
Natural products with health benefits, nutraceuticals, have shown considerable promise in many studies; however, this potential has yet to translate into widespread clinical use for any condition. Notably, many drugs currently on the market, including the first analgesic aspirin, are derived from plant [...] Read more.
Natural products with health benefits, nutraceuticals, have shown considerable promise in many studies; however, this potential has yet to translate into widespread clinical use for any condition. Notably, many drugs currently on the market, including the first analgesic aspirin, are derived from plant extracts, emphasizing the historical significance of natural products in drug development. Curcumin and resveratrol, well-studied nutraceuticals, have excellent safety profiles with relatively mild side effects. Their long history of safe use and the natural origins of numerous drugs contrast with the unfavorable reputation associated with nutraceuticals. This review aims to explore the nutraceutical potential for treating pseudoachondroplasia, a rare dwarfing condition, by relating the mechanisms of action of curcumin and resveratrol to molecular pathology. Specifically, we will examine the curcumin and resveratrol mechanisms of action related to endoplasmic reticulum stress, inflammation, oxidative stress, cartilage health, and pain. Additionally, the barriers to the effective use of nutraceuticals will be discussed. These challenges include poor bioavailability, variations in content and purity that lead to inconsistent results in clinical trials, as well as prevailing perceptions among both the public and medical professionals. Addressing these hurdles is crucial to realizing the full therapeutic potential of nutraceuticals in the context of pseudoachondroplasia and other health conditions that might benefit. Full article
(This article belongs to the Special Issue The Value of Natural Compounds as Therapeutic Agents: 2nd Edition)
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